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People with
mutations in BRCA genes or a family history of breast cancer
now have one less thing to worry about. Although their chances
of developing breast or ovarian cancer are high, new research
shows their colorectal cancer risk is about the same as that
of the general population.

Stephen B. Gruber, M.D., Ph.D.,
U-M cancer geneticist

“People carrying BRCA1 or BRCA2 mutations already have
their plates full managing a high risk of breast and ovarian
cancer,” says Stephen B. Gruber, M.D., Ph.D., a cancer
geneticist in the U-M’s Comprehensive Cancer Center.
“The good news in our study is that they don’t
have to deal with an increased risk of colorectal cancer,
as well.”

Scientists have known for years that mutations in genes called
BRCA1 and BRCA2 are associated with a much higher incidence
of breast and ovarian cancer. Studies to determine whether
BRCA mutations also increase the risk of colorectal cancer,
however, have produced mixed and inconsistent results.

In the current study, Gruber and colleagues tested blood
samples from 1,422 patients with colorectal cancer and 1,566
control subjects without colorectal cancer for mutations in
BRCA1 or BRCA2.

Study participants were selected from the population-based
Molecular Epidemiology of Colorectal Cancer (MECC) study in
northern Israel – a collaboration between Gruber and
Gad Rennert, M.D., Ph.D, of the Technion-Israel Institute
of Technology Faculty of Medicine and Carmel Medical Center
in Haifa, Israel. Colorectal cancer patients in the study
were all treated at five major hospitals in northern Israel.
They were matched with study participants without colorectal
cancer who were of the same age, sex, ethnicity and from the
same geographic area.

U-M scientists used DNA assays designed to identify three
specific mutations in BRCA1 or BRCA2 genes. Called founder
mutations, they are present in about 2.5 percent of men and
women of Ashkenazi Jewish ancestry. Of the patients with colorectal
cancer in the study, 1,002 were Ashkenazi Jews, as were 1,038
people without colorectal cancer.

“The advantage of working with founder mutations is
that we know exactly where they occur in the DNA sequence,
so it makes it makes it relatively easy to develop an assay
to identify them,” explains Bethany L. Niell, a student
in the U-M Medical School’s M.D./Ph.D. program, who
was the paper’s first author.

When they compared the results of DNA testing, U-M scientists
found no statistically significant difference between the
number of cancer patients with BRCA1 or BRCA2 mutations (24),
and the number of non-cancer controls whose DNA contained
one of these mutations (20).

“We found no strong common genetic basis between colorectal
and breast cancer,” says Gruber. “They are different
diseases with different genetic factors.”

In the second part of the study, scientists compared whether
a family history of breast cancer in a parent, sister or daughter
was associated with the development of colorectal cancer.

“We found no association between a family history of
breast cancer in a first-degree female relative and an increased
risk of colorectal cancer,” says Gruber, an assistant
professor of internal medicine and human genetics in the U-M
Medical School and an assistant professor of epidemiology
in the U-M School of Public
Health.

“Population-based studies like the MECC study allow
you to select patients and controls from the same general
population,” explains Niell. “Previous studies
may have overestimated the risk of colorectal cancer because
they used patients from high-risk families – those with
a family history of breast or ovarian cancer – who may
not be representative of the entire population.”

While current national clinical care guidelines recommend
informing BRCA1 and BRCA2 mutation carriers of an increased
risk of colorectal cancer, Gruber says physicians should advise
people with these mutations to follow colorectal cancer screening
guidelines established for the general public. “Anyone
over age 50 is at risk for colorectal cancer and screening
save lives,” he adds.

Colorectal cancer is the leading cause of deaths from cancer
in Israel and the second leading cause of cancer deaths in
the United States. Over 2,000 people are diagnosed with colorectal
cancer in Israel each year, but incidence rates vary widely
among different ethnic groups. Nearly 150,000 U.S. residents
were diagnosed with colorectal cancer in 2002.

The research was funded by the National Institutes of Health.
In addition to Gad Rennert, co-authors include Joseph D. Bonner
and Lynn P. Tomsho from the
U-M Medical School, and Ronit Almog, a study coordinator for
the Molecular Epidemiology of Colorectal Cancer study in Haifa,
Israel.